Data Resources for the Computer-Guided Discovery of Bioactive Natural Products

Abstract

Natural products from plants, animals, marine life, fungi, bacteria, and other organisms are an important resource for modern drug discovery. Their biological relevance and structural diversity make natural products good starting points for drug design. Natural product-based drug discovery can benefit greatly from computational approaches, which are a valuable precursor or supplementary method to in vitro testing. We present an overview of 25 virtual and 31 physical natural product libraries that are useful for applications in cheminformatics, in particular virtual screening. The overview includes detailed information about each library, the extent of its structural information, and the overlap between different sources of natural products. In terms of chemical structures, there is a large overlap between freely available and commercial virtual natural product libraries. Of particular interest for drug discovery is that at least ten percent of known natural products are readily purchasable and many more natural products and derivatives are available through on-demand sourcing, extraction and synthesis services. Many of the readily purchasable natural products are of small size and hence of relevance to fragment-based drug discovery. There are also an increasing number of macrocyclic natural products and derivatives becoming available for screening.

Tuning artificial intelligence on the de novo design of natural-product-inspired retinoid X receptor modulators

“…Three natural products ( Fig. 1, Table 1), namely drupanin (1) 17 , honokiol (2) 18 and bigelovin (3) 19 have been known to activate RXRs at micromolar concentrations. We have recently discovered RXR agonistic activity for valerenic acid (4), isopimaric acid (5) and dehydroabietic acid (6) by computer-assisted screening 4 .…”

“…With the aim to increase the number and quality of the designed compounds, we expanded the set of templates for transfer learning to three templates, namely valerenic acid (4), drupanin (1) and honokiol (2). 1000 de novo SMILES strings were sampled, 79% of which were valid and 49% were unique (Fig.…”

“…D rug discovery progressively employs natural products with defined bioactivities as starting points for medicinalchemistry-driven molecule optimization 1,2 . Bioactive natural products are considered potentially superior to small molecules of purely synthetic origin in terms of their unique geometries and scaffolds 3 .…”

Creating and screening natural product libraries

“…[42][43][44] Nevertheless, fewer than 20% of the core ring scaffolds discovered from natural product sources are represented in most commercially available synthetic collections or compound libraries 45 and, of more than 250 000 natural products reported, only a small portion are commercially available. 46 Ultimately, the compilation of a complementary collection of diverse source organisms resulting in wellannotated natural product extracts and fractions, should yield more structurally-diverse pure compounds from HTS for further evaluation as potential drug leads.…”

<strong></strong>LANaPD: Towards a Unified Latin America Natural Products Database

“…One of such key contributions has been the organization and analysis of chemical information of NPs, with or without biological activity, in compound databases. Over the past five years, several reviews of NP databases have been published [17][18][19][20][21]. Some of these reviews include chemoinformatic analysis of the contents, diversity, and coverage of the compounds in chemical space.…”